This is a proposal to continue the Rancho Bernardo Study (RBS) of osteoporosis, a prospective study of sex specific rates of and risk factors for bone loss and fracture in community-dwelling older adults. Men and women have had concurrent dual enelgy x-ray absorptiometry (DXA) at the hip and spine three previous times at four-year intervals. Over 1,500 men and women aged 50+ were studied in 1988-91 and 1992-95 under NIA MERIT awards. Over 1,000 are being re-evaluated with a third NIA grant in 1998-2002. Multiple behavioral and biological risk factors for osteoporosis have been assessed. Recently completed assays performed on blood obtained at earlier visits include IGF-1, IGFBP1, IL-6, C-reactive protein, PTH and 25 OH and 1,25 (OH)2 vitamin D. We have found similar bone loss rates in men and women, despite sex differences in the association of diabetes, insulin, IGF-1 and sex hormones with BMD, height loss, and fracture. We have also found sex differences in bone size, bone integrated strength (a combination of bone size and density), and kyphotic posture. Using this award, we will determine the sex-specific timing, frequency, antecedents, and consequences over age and time of (1) bone loss, (2) vertebral morphometric fractures, (3) clinical osteoporotic fractures, (4) changes in bone size and integrated strength;and (5) changes in kyphosis in 800 to 1,000 previously studied ambulatory men and women aged 50 +. We will 1) repeat DXA at the hip and spine;spine radiographs;bone size/strength estimates, and kyphosis assessment, 2) continue follow-up for new clinical fractures;and 3) reassess medical and functional status, quality of life and fall-related co-morbidities (vision, depressed mood, cognition, and muscle mass and strength). We will measure for the first time morphometric spine fractures by DXA-IVA, and serum osteoprotegerin (OPG) levels. Using these data, we will 1) assess the age and sex related pattern of change in body size, lean body mass, BMD, NTX, bone size, bone geometry, and kyphotic posture, 2) assess the independent or co-dependent predictive value of previously assayed novel or understudied risk factors (IL-6, IGF-1 &IGFBP1, PTH, vitamin D) for these changes and for incident fractures, 3) assess the consequences of fracture, and 4) develop recommendations for the diagnosis and prevention of osteoporosis in elderly men and women.